1. Field of the Invention
The present invention relates to a method of preventing or alleviating mammalian obesity.
2. Description of the Related Art
Fat cells have the ability to store fat in their cells and are typically present in the adipose tisses of the subcutaneous abdominal region, the femoral region, the gluteal region, the pectoral region and the like, and the adipose tissues which are in the abdominal cavity and in the vicinity of the mesenterium, kidney, epididymis, and the like, which are in the body of a mammal, such as a human. For example, promoting the storage of fat in fat cells generally results in an obese mammal, which is generally accompanied by an increase in body fat content and an increase in the mass of adipose tissue which is typically in the abdominal cavity of the mammal. It is knovwn that such obesity thereby induces disorders such as the impairment in glucose tolerance [Journal of Clinical Investigation, vol.72, pp. 1150 (1983)], diabetes [National Diabetes Data Group: Diabetes in America. Bethesda, Md., U.S. Dept. of Health and Human Services, (1985), Diabetes Care, vol.19, pp.613 (1996), Diabetes & Metabolisme, vol.20, pp.375 (1994), Obesity: Advances in Understanding and Treatment, Published by IBC Biomedical Library, Chapter 3.1, (1996)], hyperglycemia, hyperlipemia, hypertension [Journal of Clinical Investigation, vol.72, pp. 1150 (1983)], coronary arterial diseases [Diabetes & Metabolisme, vol.20, pp.375 (1994)], obstructive arterial sclerosis and the like [WHO Expert Committee on Diabetes Mellitus. Second report, WHO Tech Rep 646 Geneva: World Health Organization (1980)].
The fat cells are generally produced by differentiating progenitor fat cells. To differentiate progenitor fat cells into fat cells, it is essential to activate a function of a protein called Peroxisome Proliferator-Activated Receptor gamma (hereinafter refereed to as "PPAR .gamma.")[Peter Tontonoz, et al., Cell, vol.79, 1147-1156, 1994]. For example, the accumulation of fat in a fat cell can occur from having a thiazolidinedione derivative bind to PPAR .gamma. in the progenitor fat cell so that PPAR .gamma. can be activated, which induces the differentiation of the progenitor fat cell to a fat cell, and which then further expresses genes associated with fat accumulation [Jurgen of M. Lehman, et al., Journal of Biological Chemistry, vol. 270, No. 22, 12953-12956, 1995]. PPAR .gamma. is a nuclear receptor type transcription regulating factor [Issenman and Green, Nature 347-645-650 (1990)].
Accordingly, there is a demand for the development of drugs which are effieffective in suppressing die increase in body fat content and the increase in the mass of adipose tissues, by suppressing the differentiation of the progenitor fat cell to the fat cell and further tile accumulation of fat in the fat cell and, as a result, preventing or alleviating obesity. Such drugs are expected to be effective for preventing or treating various diseases derived from obesity.